A novel combination of fosfomycin/tobramycin produced by Gilead Sciences appeared safe and effective for patients with cystic fibrosis and chronic Pseudomonas infection, in a Phase 2 multicenter randomized trial of 119 patients across the U.S.
To control chronic Pseudomonas infection, cystic fibrosis patients alternate between 28 days of inhaled antibiotics and 28 days without. The “without” period is supposed to prevent Pseudomonas resistance and aminoglycoside toxicity, but aminoglycoside-resistant strains are becoming more common anyway, especially as the life expectancy of cystic fibrosis climbs.
Bruce Trapnell et al gave inhaled aztreonam to all patients for a one month run-in period, then randomized them to either inhaled fosfomycin/tobramycin (FTI) or placebo twice daily for 28 days. Those receiving FTI maintained their lung function through the month, while those getting placebo saw their FEV1 decline by ~7%. The inhaled drug did cause some dyspnea and wheezing.
Gilead Sciences is developing the combination fosfomycin/tobramycin antibiotic. The tobramycin dose is lower in the FTI product than the usual dose of tobramycin given alone; this would potentially allow continuous dosing with a lower risk of toxicity. Gilead financed this study, and their writer helped write the manuscript.
Trapnell BC et al. Fosfomycin/Tobramycin for Inhalation in Patients with Cystic Fibrosis with Pseudomonas Airway Infection. Am J Respir Crit Care Med 2012;185:171-178.